The pyrimidine compound with which the present invention is concerned has the following structural formula ##STR1## and is known as buspirone. The hydrochloride salt has been referred to in the prior art as MJ 9022-1 and as buspirone hydrochloride. Other acid addition salts thereof are named by combining "buspirone" with the appropriate word to define the acid from which it is prepared as in "buspirone hydrochloride." The latter is the United States Adopted Name (USAN); refer to J. American Med. Assoc. 225, 520 (1973).
The synthesis of the compound and the disclosure of its psychotropic properties are described in the following patents and publications.
1. Y. H. Wu, et al., J. Med. Chem., 15, 477 (1972). PA1 2. Y. H. Wu, et al., U.S. Pat. No. 3,717,634 patented Feb. 20, 1973. PA1 3. L. E. Allen, et al., Arzneium. Forsch., 24, No. 6, 917-922 (1974). PA1 4. G. L. Sathananthan, et al., Current Therapeutic Research, 18/5, 701-705 (1975). PA1 5. Y. H. Wu, et al., U.S. Pat. No. 3,976,776, patented Aug. 24, 1976.
The use of buspirone hydrochloride as an anti-anxiety agent for the treatment of neurotic patients is described in G. P. Casten, et al., U.S. Pat. No. 4,182,763 patented Jan. 8, 1980. Currently, clinical studies to support a submission to U.S. Food & Drug Administration for the use of buspirone in treatment of anxiety neurosis are being conducted.
The present invention can be distinguished from this prior art in that it involves a distinct patient population characterized by a disease state different from the anxiolytic process disclosed in the prior art.
The extrapyramidal system and its disorders are familiar to medical practitioners whose specialities are associated with neurological disorders as contrasted with psychiatric disorders addressed by buspirone prior art. For background, summaries of this area are available ranging from the very concise, e.g. cf: The Merck Manual, 14th Edition, Section 132, page 1357-1364 (1982) to detailed reviews such as Sovner and DiMascio, "Psychopharmacology: A Generation of Progress", Lipton, DiMascio, and Killam (Eds.), Raven Press, N.Y., 1978, pp. 1021-1032; and Marsden, et al., "Psychiatric Aspects of Neurological Disease", Benson and Blumers (Eds.), Grune and Stratton, N.Y., 1975, pp. 219-265.
Essentially, extrapyramidal disorders can be characterized by symptoms such as involuntary movements (tremors, tics, etc.); impairment of voluntary movement (brady-, hypo-, or akinesia); and changes in muscle tone and posture (dystonia, muscle rigidity, dysequilibrium). Parkinsonism, neuroleptic-induced extrapyramidal symptoms (EPS), and tardive dyskinesia are examples of discrete extrapyramidal motor disorders. Such disorders may arise spontaneously or as a consequence of drug administration.